The present invention relates to new derivatives of eryrthromycin, their preparation process and their use as medicaments.
A subject of the invention is, as new chemical products, the compounds of formula (I) 
in which X represents a hydrogen atom or a halogen atom and Z represents a hydrogen atom or the remainder of an acid as well as their addition salts with acids.
Among the addition salts with acids, the salts formed with acetic, propionic, trifluoroacetic, maleic, tartaric, methanesulphonic, benzenesulphonic, p-toluenesulphonic acids and particularly stearic, ethylsuccinic or laurylsulphonic acids, can be mentioned.
The halogen atom is for example a chlorine or fluorine atom and preferably a fluorine atom.
A more particular subject of the invention is the compounds of formula (I) in which Z represents a hydrogen atom.
A more particular subject of the invention is the compounds, the preparation of which is given hereafter in the experimental part.
The products of general formula (I) have a very good antibiotic activity on gram ⊕bacteria such as staphylococci, streptococci, pneumococci.
The products are particularly active on strains which are resistant to erythromycin such as for example Streptococcus pyogenes and Streptococcus pneumoniae and S. aureus which have an inducible resistance to erythromycin.
The compounds of the invention can therefore be used as medicaments in the treatment of germ-sensitive infections and in particular, in that of staphylococcia such as staphylococcal septicaemias, malignant staphylococcia of the face or skin, pyodermitis, septic or suppurating wounds, boils, anthrax, phlegmons, erysipelas and acne, staphylococcia such as primitive or post-influenzal acute angina, bronchopneumonia, pulmonary suppuration, streptococcia such as acute angina, otitis, sinusitis, scarlatina, pneumococcia such as pneumonia, bronchitis, and diphtheria. The products of the present invention are also active against infections caused by germs such as Haemophilus influenzae.
Therefore a subject of the invention is the compounds of formula (I) as medicaments.
More especially a subject of the invention is, as medicaments, the compounds indicated above as preferred compounds.
A subject of the invention is also the pharmaceutical compositions containing at least one of the medicaments defined above, as active ingredient.
These compositions can be administered by buccal, rectal, parenteral route, or by local route as a topical application on the skin and mucous membranes, but the preferred administration route is the buccal or injectable route. They can be solids or liquids and be presented in the pharmaceutical forms commonly used in human medicine, such as for example, plain or sugar-coated tablets, gelatin capsules, granules, suppositories, injectable preparations, ointments, creams, gels; they are prepared according to the usual methods. The active ingredient or ingredients can be incorporated with the excipients usually used in these pharmaceutical compositions such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents, preservatives.
These compositions can also be presented in the form of a powder intended to be dissolved extemporaneously in an appropriate vehicle, for example, apyrogenic sterile water.
The dose administered is variable according to the affection treated, the patient in question, the administration route and-the product considered. It can be, for example, comprised-between 50 mg and 3000 mg per day by oral or injectable route for an adult for the preferred products.
A subject of the invention is also a preparation process. characterized in that a compound of formula (II): 
in which X retains its previous meaning and OM represents the remainder of an acyl radical is subjected to the action of a compound of formula (III) 
in order to obtain the corresponding compound of formula (IA) then if desired the compound of formula (IA) is subjected to the action of an agent of the hydroxyl function in position 2xe2x80x2 and/or if appropriate, to the action of an acid in order to form the salt.
the reaction of the compound of formula (II) with the compound of formula (III) takes place in a solvent such as for example acetonitrile, dimethylformamide or also tetrahydrofuran, dimethoxy ethane or dimethylsulphoxide,
the hydrolysis of the ester function in position 2xe2x80x2 is carried out using methanol or aqueous hydrochloric acid,
the salification is carried out using acids according to standard processes.
The compounds of formula (II) in which X represents a hydrogen atom, which are used as starting products are described and claimed in European Patent Application 0 596 802.
The compounds of formula (II) which are used as starting products in which X represents a fluorine atom can be prepared as indicated hereafter in the experimental part.